None listed
Conditions
Brief summary
This study involves treatment with a standard chemotherapy for melanoma in combination with immune therapy. Fotemustine is a chemotherapy drug that is approved for use in metastatic melanoma. It has been shown to produce responses in 15 % of patients. Other benefits include delaying the onset of metastases to the brain, with its major side effects including nausea and vomiting (generally well controlled with current anti-nausea treatments) and low blood counts that could lead to a risk of bleeding and/or infections. The main aim of the study is to determine the number of patients who respond to successive treatment with chemotherapy followed by vaccine therapy and Ipilimumab in patients with previously untreated stage IV metastatic melanoma. It is planned to include 50 patients with stage IV metastatic melanoma in this study over a 3 year period. Who is it for? You may be eligible for this study if you have metastatic stage IV metastatic melanoma, provide written informed consent , an ECOG performance status of 0, 1 or 2, are deemed by your physician to be able to safely undergo leukapheresis, are aged greater than or equal to 16 years, have a life expectancy estimated to be greater than 4 months, and are able to provide a tumour sample or an alternative source of tumour antigen – as arranged by your treating hospital or facility. Trial Details: There are two components to the immune therapy that the patients will receive. One is treatment with a vaccine comprised of the patients’ own Dendritic Cells (immune system boosters, also known as DC’s), treated in the laboratory with their own tumour (autologous melanoma), plus a number of agents known to help stimulate the immune system. Previous studies have shown response rates (meaning melanoma shrinkage) in 10-25 % of cases at best. The overall survival benefits have not been assessed in large numbers of patients. However in a small trial of 11 patients receiving vaccines similar to (but not identical to) the vaccine being used in this study, 3 remain alive 5 years after study enrolment. The second component of the immune therapy is an antibody (Ipilimumab) that unblocks the protective mechanisms that normally operate to prevent the immune system recognising and damaging one’s own body. With this protective mechanism in place, it is very difficult for vaccines to boost the immune system to recognise and kill the melanoma. Ipilimumab has been shown to prolong survival in patients with metastatic melanoma who have previously failed chemotherapy. Of patients previously treated with chemotherapy and then treated with Ipilimumab, 44% were still alive one year after starting Ipilimumab treatment. In comparison of the patients who did not receive Ipilimumab only 25% were still alive after one year. By combining a vaccine with Ipilimumab, it is expected that the boosted immune system (resulting from the vaccines) will not be prevented from recognising and killing the melanoma.
Interventions
Participants will receive 3 intravenous infusions of Fotemustine 100mg/m2/week for three weeks followed by 3 intradermal vaccinations with 3-6x106 mature, autologous DC treated with tumour lysate (2ug of protein per ml) and immune adjuvants (Zometa, OK432, and KRN7000) at 2 weekly intervals. The participant will then receive four intravenous infusions of Ipilimumab at 3mg/kg per dose at three weekly intervals, concurrently with further DC vaccination. After completion of Ipilimumab, patients wil
Participants will receive 3 intravenous infusions of Fotemustine 100mg/m2/week for three weeks followed by 3 intradermal vaccinations with 3-6x106 mature, autologous DC treated with tumour lysate (2ug of protein per ml) and immune adjuvants (Zometa, OK432, and KRN7000) at 2 weekly intervals. The participant will then receive four intravenous infusions of Ipilimumab at 3mg/kg per dose at three weekly intervals, concurrently with further DC vaccination. After completion of Ipilimumab, patients will then receive at least four further DC vaccinations at fortnightly intervals until study completion or disease progression.
Sponsors
Andrew Nicol
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Patients with metastatic stage IV metastatic melanoma and measurable disease as defined by the most recently published RECIST criteria. 2) Written informed consent 3) ECOG performance status 0, 1 or 2 4) Subject judged to be able to safely undergo leukapheresis 5) Age greater than or equal to 16 years. 6) Life expectancy estimated to be greater than 4 months 7) Availability of tumour sample or an alternative source of tumour antigen
Exclusion criteria
1) Any concurrent therapy with possible activity against the patient’s malignancy (local radiotherapy on lesions not essential for study evaluation is allowed) 2) Concurrent therapy with any agent known to have immune modulating activity 3) Any therapy with possible activity against the patient’s malignancy in the month preceding administration of first dose of study therapy 4) Patient unable to undergo leukapheresis due to serious co-existing medical conditions (particularly cardiac or cardiovascular) or for other reasons 5) ECOG > 2 6) Pregnant or breast feeding or at risk for becoming pregnant within 3 months of enrolment 7) HIV, Hepatitis B or Hepatitis C positive 8) Patients with history of autoimmune disease affecting the liver, gastrointestinal tract (e.g. ulcerative colitis or Crohn's disease), neurological system (including Guillaine Barre Syndrome and Myasthenia Gravis) and autoimmune pituitary or adrenal disease. 9) Active CNS disease requiring steroids
Outcome results
None listed